Both murine and human epidermal growth factors (EGFs) are known to cause precocious opening of the eyelids in newborn mice. Another set of peptides that are structurally and functionally homologous to murine and human EGFs are the murine and human type-alpha transforming growth factors (TGF-alpha s), TGF-alpha s have been found in many cancer cells and it has been suggested that their autocrine action may play an important part in malignant transformation. In several in vitro systems murine and human TGF-alpha s are functionally interchangeable with murine and human EGFs. However, the in vivo activity of the TGF-alpha s has not been characterized, as only small amounts of these peptides were available until recently. The cloning of the gene for human TGF-alpha and its expression in Escherichia coli now allow us to demonstrate that human TGF-alpha is as active as murine EGF in promoting eyelid opening in newborn mice. Furthermore, we show in a dose-dependent eyelid opening assay that human EGF is as potent as its murine homologue with respect to this biological property.